BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.
BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.
Authors: Divij Mathew; Josephine R Giles; Amy E Baxter; Derek A Oldridge; Allison R Greenplate; Jennifer E Wu; Cécile Alanio; Leticia Kuri-Cervantes; M Betina Pampena; Kurt D'Andrea; Sasikanth Manne; Zeyu Chen; Yinghui Jane Huang; John P Reilly; Ariel R Weisman; Caroline A G Ittner; Oliva Kuthuru; Jeanette Dougherty; Kito Nzingha; Nicholas Han; Justin Kim; Ajinkya Pattekar; Eileen C Goodwin; Elizabeth M Anderson; Madison E Weirick; Sigrid Gouma; Claudia P Arevalo; Marcus J Bolton; Fang Chen; Simon F Lacey; Holly Ramage; Sara Cherry; Scott E Hensley; Sokratis A Apostolidis; Alexander C Huang; Laura A Vella; Michael R Betts; Nuala J Meyer; E John Wherry Journal: Science Date: 2020-07-15 Impact factor: 47.728
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Authors: Jimmykim Pham; Sarah Meyer; Catherine Nguyen; Analee Williams; Melissa Hunsicker; Ian McHardy; Inessa Gendlina; D Yitzchak Goldstein; Amy S Fox; Angela Hudson; Paul Darby; Paul Hovey; Jose Morales; James Mitchell; Karen Harrington; Mehrdad Majlessi; Joshua Moberly; Ankur Shah; Andrew Worlock; Marion Walcher; Barbara Eaton; Damon Getman; Craig Clark Journal: J Clin Microbiol Date: 2020-09-22 Impact factor: 5.948
Authors: Vineet Agarwal; A J Venkatakrishnan; Arjun Puranik; Christian Kirkup; Agustin Lopez-Marquez; Douglas W Challener; Elitza S Theel; John C O'Horo; Matthew J Binnicker; Walter K Kremers; William A Faubion; Andrew D Badley; Amy W Williams; Gregory J Gores; John D Halamka; William G Morice; Venky Soundararajan Journal: Cell Death Discov Date: 2020-12-02
Authors: Philippe Selhorst; Sabrina Van Ierssel; Jo Michiels; Joachim Mariën; Koen Bartholomeeusen; Eveline Dirinck; Sarah Vandamme; Hilde Jansens; Kevin K Ariën Journal: Clin Infect Dis Date: 2020-12-14 Impact factor: 9.079
Authors: Sjoerd M Euser; Tieme Weenink; Jan M Prins; Milly Haverkort; Irene Manders; Steven van Lelyveld; Bjorn L Herpers; Jan Sinnige; Jayant Kalpoe; Dominic Snijders; James Cohen Stuart; Fred Slijkerman Megelink; Erik Kapteijns; Jeroen den Boer; Alex Wagemakers; Dennis Souverein Journal: Diagnostics (Basel) Date: 2022-03-15